Effects of slurry ice treatment on the physicochemical changes and proteome of large yellow croaker (Larimichthys crocea).

Large yellow croaker (Larimichthys crocea) is susceptible to oxidative denaturation during storage. This work is to investigate the quality alterations by analyzing its physicochemical changes and proteomics throughout preservation under refrigeration, frozen, and slurry ice (SI) conditions. Results revealed that the freshness of large yellow croaker, as evaluated by indicators such as total volatile basic nitrogen, total viable count, and thiobarbituric acid reactive substances, was well maintained while stored in the SI group. Meanwhile, the water distribution in the muscle tissue of group SI exhibited slower fluctuations, thereby preserving the integrity of fish muscle cells. Based on label-free proteomic analysis, a considerable downregulation was observed in the mitogen-activated protein kinase (MAPK) signaling pathway, indicating that SI decelerated this metabolic pathway and effectively delayed the deterioration of muscle. Therefore, the application of SI provides potential for maintaining the quality stability of large yellow croaker.

Preliminary Study of Radionuclide-Labeled MerTK-Targeting PET Imaging Agents for the Diagnosis of Melanoma.

MerTK PET imaging holds potential as a promising approach for assessing tumor aggressiveness and monitoring treatment response. In this study, we synthesized a series of 18F- and 68Ga-labeled tracers derived from MerTK inhibitors for detection of MerTK expression. Among the synthesized agents, the dimeric compounds [68Ga]10 and [68Ga]12 demonstrated good in vivo and in vitro stability, high affinities to the MerTK receptor, and good MerTK-targeting specificity. Notably, [68Ga]10 exhibited a tumor uptake of 2.6 ± 0.2%ID/g at 1 h p. i. in B16F10 tumor-bearing mice, nearly tripling the uptake of its monomeric counterpart [68Ga]3. A similar enhancement was observed with [68Ga]12 compared to its monomeric analog [68Ga]6. Additionally, [18F]14 achieved a tumor uptake of 7.6 ± 0.5%ID/g at 2 h p. i., outperforming the previously reported [18F]15. Biodistribution analysis further validated the results, highlighting their potential for clinical investigation.

Role of KLF4 and SIAT7A interaction accelerates myocardial hypertrophy induced by Ang II.

Sialylation catalysed by sialyltransferase 7A (SIAT7A) plays a role in the development of cardiac hypertrophy. However, the regulatory mechanisms upstream of SIAT7A in this context remain poorly elucidated. Previous study demonstrated that KLF4 activates the SIAT7A gene in ischemic myocardium by binding to its promoter region. Nevertheless, the potential involvement of KLF4 in regulating SIAT7A expression in Ang II-induced hypertrophic cardiomyocytes remains uncertain. This study seeks to deepen the underlying mechanisms of the KLF4 and SIAT7A interaction in the progression of Ang II-induced cardiac hypertrophy. The results showed a concurrent increase in SIAT7A and KLF4 levels in hypertrophic myocardium of essential hypertension patients and in hypertrophic cardiomyocytes stimulated by Ang II. In vitro experiments revealed that reducing KLF4 levels led to a decrease in both SIAT7A synthesis and Sialyl-Tn antigen expression, consequently inhibiting Ang II-induced cardiomyocyte hypertrophy. Intriguingly, reducing SIAT7A levels also resulted in decreased KLF4 expression and suppression cardiomyocyte hypertrophy. Consistent with this, elevating SIAT7A levels increased KLF4 expression and exacerbated cardiomyocyte hypertrophy in both in vivo and in vitro experiments. Additionally, a time-course analysis indicated that KLF4 expression preceded that of SIAT7A. Luciferase reporter assays further confirmed that modulating SIAT7A levels directly influenced the transcriptional activity of KLF4 in cardiomyocytes. In summary, KLF4 expression is upregulated in cardiomyocytes treated with Ang II, which subsequently induces the expression of SIAT7A. The elevated levels of SIAT7A, in turn, enhance the transcription of KLF4. These findings suggest a positive feedback loop between KLF4 and SIAT7A-Sialyl-Tn, ultimately promoting Ang II-induced cardiac hypertrophy.

Respiration-Induced Organ Motion Compensation: A Review.

PURPOSE: Motion of organs in the abdominal and thoracic cavity caused by respiration is a major issue that affects a wide range of clinical diagnoses or treatment outcomes, including radiotherapy, high-intensity focused ultrasound ablation, and many generalized percutaneous needle interventions. These motions pose significant challenges in accurately reaching the target even for the experienced clinician. METHODS: This review was conducted through comprehensive search on IEEE Explore, Google Scholar, and PubMed. RESULTS: Diverse methods have been proposed to compensate for this motion effect to enable effective surgical operations. This review paper aims to examine the current respiratory motion compensation techniques used across the clinical procedures of radiotherapy, high-intensity focused ultrasound, and percutaneous needle procedures. CONCLUSION: The complexity of respiratory-induced organ motion and diversity of areas for which compensation can be applied allows for a variety of methods to be implemented. This review aims to serve as inspiration for the future development of new systems to achieve clinical relevance.

Mitigating greenhouse gas emission and enhancing fermentation by phosphorus slag addition during sewage sludge composting.

During the composting of sewage sludge (SS), a quantity of greenhouse gases has been produced. This study aimed to clarify the microbial mechanisms associated with the addition of industrial solid waste phosphorus slag (PS) to SS composting, specifically focusing on its impact on greenhouse gas emissions and the humification. The findings indicated that the introduction of PS increased the temperature and extended the high-temperature phase. Moreover, the incorporation of 10% and 15% PS resulted in a decrease of N2O emissions by 68.9% and 88.6%, respectively. Microbial diversity analysis indicated that PS improved waste porosity, ensuring the aerobic habitat. Therefore, the environmental factors of the system were altered, leading to the enrichment of various functional bacterial species, such as Firmicutes and Chloroflexi, and a reduction of pathogenic bacterium Dokdonella. Consequently, incorporating PS into SS composting represents an effective waste treatment strategy, exhibiting economic feasibility and promising application potential.

Xiaobugan decoction prevents CCl4-induced acute liver injury by modulating gut microbiota and hepatic metabolism.

BACKGROUND: The liver plays a crucial role in detoxification and metabolism. When its capacity to metabolize foreign substances is exceeded, it can lead to acute liver injury (ALI). Therefore, preventing liver disease and maintaining daily liver health are of utmost importance. Xiaobugan Decoction (XBGD), a traditional Chinese medicine (TCM) formula, is recorded in 'Fuxingjue', is used in folk practice to promote liver health and regulate respiration. However, the hepatoprotective mechanisms of XBGD remained unclear. PURPOSE: We investigated the prophylactic and hepatoprotective effects of XBGD and explored its related molecular mechanisms using a mouse model of carbon tetrachloride (CCl4)-induced ALI. STUDY DESIGN AND METHODS: XBGD composition was determined using analytical methods, and the main compounds were identified using ultra-high-performance liquid chromatography coupled with Q-Exactive focus mass spectrum (UHPLC-QE-MS) and high-performance liquid chromatography (HPLC). A CCl4-induced L02 cell injury model was employed to explore the protective effects of XBGD on liver cells, and a CCl4-induced ALI mouse model was used to investigate the hepatoprotective effects of XBGD. RESULTS: Cellular experiments demonstrated that XBGD had a protective function against L02 cell damage by increasing cell viability, restoring alanine aminotransferase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD) levels, reducing malondialdehyde (MDA) content, and improving mitochondrial membrane potential (ΔΨm). In the mouse ALI model, XBGD prevented ALI by reducing ALT, AST, and alkaline phosphatase (ALP) levels and inhibiting oxidative stress. Quantitative real-time polymerase chain reaction (qPCR), immumohistochemical staining and western blotting results revealed that XBGD exerted hepatoprotective effects by reducing inflammatory responses and inhibiting cell apoptosis. Furthermore, 1H-NMR metabolomics indicated that XBGD regulates hepatic and intestinal metabolism, whereas 16S rDNA sequencing demonstrated the regulatory effects of XBGD on the gut microbiota. Correlation analysis highlighted the close relationship among gut microbiota, metabolites, and ALI indicators. CONCLUSIONS: XBGD is a promising TCM for the prevention of CCl4-induced ALI via regulation of microbiota and metabolism. This study provides a new perspective on the development of hepatoprotective measures and the prevention of liver disease in daily life.

Pr6O11 modification effectively enhancing sodium storage for Na3V2(PO4)3 batteries.

Na3V2(PO4)3 (NVP) is one of the most promising cathode materials for sodium-ion batteries (SIBs) due to its robust three-dimensional framework, high tunability, and relatively high Na+ intercalation potentials. However, its utility is generally constrained by low conductivity, inefficient charge transfer, and subpar interface kinetics. This work presents an efficient and simple method to address these issues. We innovatively modified the NVP surface with Pr6O11 nanoparticles, a negative temperature coefficient (NTC) thermosensitive material, to enhance interface compatibility with electrolytes and improve conductivity. This modification significantly enhances the overall sodium-ion storage performance. Specifically, the optimized NVP-2 %Pr6O11 electrode exhibits excellent electrochemical properties with the aid of an optimized conductivity network compared to the unmodified NVP. Cycled at an 8C current density, the NVP-2 %Pr6O11 electrode achieves high specific capacities of 102.6 mAh·g-1 at 27 °C and 95.6 mAh·g-1 at 45 °C. After 1000 cycles, the capacity retention rates are 81.18 % and 78.97 %, respectively, significantly higher than the 20.59 % and 14.99 % of pure NVP. In coin full-battery testing, the NVP-2 %Pr6O11 electrode retains 89.76 % capacity after 500 cycles at 8C. In addition, the assembled The NVP-2 %Pr6O11//HC pouch full battery exhibits better sodium-ion storage and thermal safety performance compared to the NVP-SP//HC battery. This simple modification strategy provides an effective insight into the application of NVP electrodes in energy storage.

Correction: A novel nano delivery system targeting different stages of osteoclasts.

Correction for 'A novel nano delivery system targeting different stages of osteoclasts' by Bosong Zhang et al., Biomater. Sci., 2022, 10, 1821-1830, https://doi.org/10.1039/D2BM00076H.

Phosphorus modifies the association between body mass index and uric acid: Results from NHANES 2007-2018.

INTRODUCTION: Studies in recent years have shown that high uric acid causes harm to the human body, which has become a serious public health problem. Elevated serum uric acid has been shown to be associated with obesity, but the relationship between BMI and uric acid (UA) remains controversial. Although the association between BMI and UA has been well studied, the effect of phosphorus levels in vivo on this association remains unclear. This study aimed to determine the relationship between BMI and serum uric acid and the effect of phosphorus on the relationship between the two. RESEARCH DESIGN AND METHODS: The present study analyzed data from the National Health and Nutrition Examination Survey (NHANES) continuous 2007-2018 cycle. We included 10786 participants aged 20 years and over. Multivariable linear regression was performed to assess the association between BMI and serum uric acid. phosphorus was stratified into low phosphorus (<3.3 mg/dl), middle phosphorus (3.3-3.9 mg/dl) and high phosphorus (>3.9 mg/dl). Correction of the effect of phosphorus was assessed by testing the interaction between BMI and UA in multivariate linear regression. RESULTS: In this cross-sectional study, we found that BMI was positively associated with UA in the female population but not significantly in the male population or in the total population. In multiple regression analysis, UA was 0.51 higher in the highest female BMI group than in the lowest group (p = 0.0001). The relationship between BMI and UA differed significantly by gender under the influence of phosphorus, with men and women in Model II having a greater elevation of UA in men than in women within most groups. (BMI >30, phosphorus >3.9 mg/dl, ß:0.83 95% CI: 0.43, 1.23 vs ß: 0.79 95% CI: 0.30, 1.29). In addition, phosphorus significantly altered the positive association between BMI and UA in most models. CONCLUSION: Our results indicate significant associations between BMI and uric acid in women, with higher BMI values likely to be associated with a higher risk of hyperuricemia, suggesting that uric acid levels in obese people should be closely monitored in clinical practice. Phosphorus and BMI have an interactive effect in elevating UA and should be noted as indicators of phosphorus in clinical practice.

Spectral reconstruction from RGB image to hyperspectral image: Take the detection of glutamic acid index in beef as an example.

The use of spectral reconstruction (SR) to recovery RGB images to full-scene hyperspectral image (HSI) is an important measure to achieve real-time and low-cost HSI applications. Taking the detection of glutamic acid index for 360 beef samples as an example, the feasibility of using 11 state-of-the-art reconstruction algorithms to achieve RGB to HSI in complex food systems was investigated. The multivariate correlation analysis was used to prove that RGB is a projection of three-channel comprehensive coverage wide-band information. The comprehensive quality attributes (PSNR-Params-FLOPS) was proposed to determine the optimal reconstruction model (MST++, MST, MIRNet, and MPRNet). Moreover, SSIM values and t-SNE were introduced to evaluate the consistency of the reconstruction results. Finally, Lightweight Transformer was used to establish the detection models of Raw-HSI, RGB and SR-HSI for the prediction of glutamic acid index for beef. The results showed that the MST++ model exhibited the best performance in SR, with RMSE, PSNR, and SSIM values of 0.015, 36.70, and 0.9253, respectively. Meanwhile, the prediction effect of MST++ (R2P = 0.8422 and RPD = 2.46) reconstructed was close to the Raw-HSI (R2P = 0.8526 and RPD = 2.69). The results provide practical application scenarios and detailed analysis ideas for RGB-to-HSI.

The Association Between Cognitive Function and Oral Health in Home Dwellers and Nursing Home Residents: The HUNT Study.

OBJECTIVES: To evaluate the relationships of cognitive function and care dependency with oral health in a Norwegian older adult population. METHODS: This cross-sectional study included 2623 participants aged 70 and older from the fourth wave of the Trøndelag health study (HUNT4 70+) and the city of Trondheim (Trondheim 70+). Neurocognitive disorders (NCDs) were diagnosed by clinical experts according to the DSM-5 framework. Care dependency referred to nursing home residency. Oral health was assessed by using the Revised Oral Assessment Guide-Jönköping (ROAG-J). Individuals were considered as 'having oral problem' if the score was two or three in at least one of the nine ROAG-J items. Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs). RESULTS: The prevalence of having oral problems was 19% higher in participants with NCDs than those with normal cognitive function after adjusting for potential confounders (PR 1.19, 95% CI: 1.09-1.29). Further analysis showed a higher prevalence of having oral problems for home dwellers with NCDs (PR 1.23, 95% CI: 1.13-1.33) and nursing home residents (PR 1.32, 95% CI: 1.20-1.45) compared to home dwellers with normal cognitive function. CONCLUSIONS: NCDs were associated with an increased prevalence of oral problems in this Norwegian older adult population. The study suggests the need for increasing oral care for home dwellers with NCDs and nursing home residents.

Response and adaptation of Chlorella pyrenoidosa to 6PPD: Physiological and genetic mechanisms.

The extensive contamination of the tire antidegradant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) in aquatic environments have raised concerns about its potential threats to aquatic organisms. Here, the responses of green algae Chlorella pyrenoidosa (C. pyrenoidosa) to 6PPD exposure were investigated for the first time. The growth of C. pyrenoidosa experienced three sequential phases, including inhibition, recovery and stimulation. Physiological and transcriptome analysis suggested that the growth inhibition was associated with the suppressed nitrogen assimilation and amino acid biosynthesis pathways, among which nitrate transporter (NRT) 2.1 was a key target of 6PPD. Molecular docking revealed the steadily binding of 6PPD to the substrate entry region of NRT 2.1 via hydrogen bonds and π - cation interaction, blocking the acquisition of extracellular inorganic nitrogen. Along with the removal of 6PPD through abiotic processes and biodegradation, an adaptive metabolic shift in cells not only facilitated growth recovery but also triggered a compensatory stimulation phase. With regard to microalgal adaptation, upregulated DNA replication and repair pathways served to maintain the integrity of the genetic information, enhanced photosynthesis cascades and central carbon metabolism improved carbon flux and energy conversion to microalgal biomass, recovered amino acid biosynthesis produced essential proteins for multiple metabolisms. The results provide new insights into microalgal molecular responses to 6PPD exposure, facilitating a better understanding of ecological consequences of 6PPD in the environment.

Response of transporter proteins activities to Cd distribution in two wild rice roots.

To investigate the characteristics of Cd transport and distribution in the wild rice roots, Oryza rufupogon Griff. and Oryza officinalis Wall. were used at research materials. Pot experiment was conducted to study the effects of different concentrations of Cd (0, 1, 5, 15 and 30 mg∙kg-1) treatments on the root pectin content, root pectin methyl esterase(PME) activity, Cation/proton exchanger(CAX), heavy metal ATPase(HMA) and ATP-binding cassette protein(ABC) activities of wild rice. The difference in Cd flow rate of wild rice root was investigated through non-invasive micro-test technique (NMT). The results showed that the Cd in roots tended to increase with the increase of Cd treatment concentrations. Compared to the CK treatment (0 mg∙kg-1 Cd), the root pectin content of O. rufupogon and O. officinalis under 30 mg∙kg-1 Cd stress were significantly increased by 126.73 % and 109.69 %, respectively. The distribution of Cd contents in wild rice roots were all greater than those in shoots. Under Cd stress, the translocation factor of O. rufupogon (0.46-1.44) were all higher than those of O. officinalis (0.15-0.37). The Cd transport capacity in O. rufupogon was more stronger than in O. officinalis. The Cd content in the xylem sap of O. officinalis was lower than that of O. rufupogon. Compared to the CK, CAX and ABC activities in O. officinalis root under 30 mg∙kg-1 Cd treatment were significantly increased by 11.03 % and 2.37 %, respectively. HMA activity in O. rufupogon root was significantly increased by 4.95 %. Cd flow rate in the root xylem of O. officinalis was higher than that of O. rufupogon. In root cells, the subcellular distribution of Cd contents showed cell wall > soluble components> organelles. With the Cd treatment concentrations increased, the percentage of Cd content in the soluble fractions of the root cells of wild rice showed an increasing. In general, the result showed that O. officinalis immobilized more Cd in the roots by influencing the pectin methyl esterification reaction through PME activity. Under high Cd stress, Cd was immobilized in root cell vacuoles of O. officinalis by enhancing roots CAX and ABC activities, whereas HMA activities were enhanced of O. rufupogon to reduce the damage caused by Cd.

Effects of probiotics on the prevention and treatment of children with allergic rhinitis: a meta-analysis of randomized controlled trials.

Background and aim: Recent studies have demonstrated the anti-allergic effects of probiotics in humans. However, their role in preventing and treating pediatric allergic rhinitis has not been thoroughly investigated. This study aimed to systematically review the efficacy and preventive effects of probiotics on pediatric allergic rhinitis. Methods: We systematically searched PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science databases for all relevant studies on probiotics and pediatric allergic rhinitis. Studies meeting the inclusion criteria were included, data were extracted, and meta-analyses were performed. Results: A total of 28 studies with 4,765 participants were included in this study. The pooled results showed that the use of probiotics was associated with a significant improvement in total nose symptom scores (SMD, -2.27; 95% CI, -3.26 to -1.29; P < 0.00001), itchy nose scores (SMD, -0.44; 95% CI, -0.80 to -0.07; P = 0.02), sneezing scores (SMD, -0.47; 95% CI, -0.84 to -0.10; P = 0.01), eye symptoms (SMD, -3.77; 95% CI, -5.47 to -2.07; P < 0.00001), and Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (SMD, -2.52; 95% CI, -4.12 to -0.92; P < 00001). However, the use of probiotics was not associated with the incidence of allergic rhinitis (RR, 0.9; 95% CI, 0.74-1.08; P = 0.26). Conclusions: The present study demonstrated that probiotics were effective and safe for improving pediatric allergic rhinitis symptoms and quality of life. However, probiotics could not prevent pediatric allergic rhinitis.

A constitutional isomer selective chemical proteomic strategy for system-wide profiling of protein lysine 5-hydroxylation.

Lysine 5-hydroxylation (5-Hyl) has been well recognized as an essential protein post-translational modification regulating cellular structural stability, RNA alternative splicing and epigenetic gene expression. System-wide enrichment and quantification of 5-Hyl targets have been challenging due to their chemical inert nature and difficulties in differentiating structural isomers in a complex biological sample. Here, we report the development of an efficient chemical proteomic workflow for affinity enrichment and constitutional isomer specific profiling of endogenous 5-Hyl substrates based on highly selective periodate chemistry. Our study confidently identified over 1600 5-Hyl sites on 630 proteins in human 293T cells, revealing functional significance of the modification in protein structure, transcription and chromatin regulation. Analysis of histone 5-Hyl sites showed that histones H2B and H1 are major targets of the 5-hydroxylysine epigenetic mark. Quantitative proteomic analysis through our chemical enrichment workflow identified specific 5-Hyl substrate proteins mediated by the overexpression of Jumonji-domain containing protein 6 (JMJD6). Our study uncovered two cancer-relevant alternative splice isoforms of JMJD6 that regulate 5-Hyl proteins in distinct cellular pathways, providing unique insights into the functional roles of JMJD6 alternative splicing in transcriptional regulation and cellular development.

Lactic acid bacteria sequential fermentation improves viable counts and quality of fermented apple juice via generating two logarithmic phases.

This study investigated the impact of lactic acid bacteria (LAB) sequential fermentation on viable counts and apple juice quality. The optimal fermentation conditions were obtained by a step-by-step optimization process, including pH 4.5, temperature 37 °C, the second inoculation time 16 h, total fermentation time 40 h and fermentation sequence (first 21,805 + 21,828, second 20,241). Under the optimal conditions, sequential fermentation allowed LAB to experience two logarithmic phases, increasing viable counts to 1.38 × 108 CFU/mL, exceeding simultaneous fermentation for 24 h and 40 h by 4.10 × 107 CFU/mL and 5.40 × 107 CFU/mL, respectively. This process enhanced sugar utilization, yielding more lactic acid and polyphenols. Furthermore, sequential fermentation improved DPPH (71.71 %) and ABTS (84.79 %) scavenging rates, and enriched volatile compounds, particularly beta-Damascenone, potentially contributing to floral and richer apple flavor. Sequential fermentation also achieved optimal sensory acceptability. This study proposes a novel strategy for high-density LAB fermentation to produce high-quality apple juice.

NLRP3 deficiency improves bone healing of tooth extraction sockets through SMAD2/3-RUNX2 mediated osteoblast differentiation.

Impaired bone healing following tooth extraction poses a significant challenge for implantation. As a crucial component of the natural immune system, the NLRP3 inflammasome is one of the most extensively studied Pattern-Recognition Receptors (PRRs), and is involved in multiple diseases. Yet, the role of NLRP3 in bone healing remains to be clarified. Here, to investigate the effect of NLRP3 on bone healing, we established a maxillary first molar extraction model in wild-type (WT) and NLRP3KO mice using minimally invasive techniques. We observed that NLRP3 was activated during the bone repair phase, and its depletion enhanced socket bone formation and osteoblast differentiation. Moreover, NLRP3 inflammasome activation was found to inhibit osteogenic differentiation in alveolar bone-derived mesenchymal stem cells (aBMSCs), an effect mitigated by NLRP3 deficiency. Mechanistically, we established that SMAD2/3-RUNX2 signaling pathway is a downstream target of NLRP3 inflammasome activation, and SMAD2/3 knockdown partially reversed the significant decrease in expression of RUNX2, OSX, and ALP induced by NLRP3. Thus, our findings demonstrate that NLRP3 negatively modulates alveolar socket bone healing and contribute to the understanding of the NLRP3-induced signaling pathways involved in osteogenesis regulation.

The Prognostic Utility of the Triceps Skinfold Thickness Albumin Index in Colorectal Cancer Patients with Cachexia.

PURPOSE: To develop a simple and convenient inflammation-nutrition-adiposity biomarker to complement the TNM staging system, further assess the prognosis of patients with colorectal cancer cachexia. METHODS: This study was a multi-centre cohort study. The triceps skinfold thickness-albumin index (TA) was calculated by combining the triceps skinfold thickness (TSF) and serum albumin levels. Kaplan-Meier analysis and Cox proportional risk regression models were used to assess the relationship between the TA and all-cause mortality. Internal validation was carried out. RESULTS: We included 1025 patients with colorectal cancer cachexia, 61.2% of whom were male, with a mean age of 58.91 (12.45) years. As the TA increased, overall mortality decreased in female patients (hazard ratio [HR], 0.95) but not in male patients (HR, 0.99). Multivariate Cox analysis showed that patients in the normal TA group had a significantly lower risk of death than those in the low TA group (HR, 0.53, 95% CI, 0.40-0.72). Patients with a normal TA had a lower risk of malnutrition, poor quality of life, and poor short-term prognosis than those with a low TA. CONCLUSIONS: TA index enables clinicians to assess the prognosis of patients as early as possible to improve the survival of patients with colorectal cancer cachexia.

A derivative of tanshinone IIA and salviadione, 15a, inhibits inflammation and alleviates DSS-induced colitis in mice by direct binding and inhibition of RIPK2.

Inflammatory bowel diseases (IBDs) are chronic inflammatory conditions primarily affecting the gastrointestinal tract. Previous studies established the role of the NF-κB signaling pathway in the development of IBDs, suggesting that anti-inflammatory therapies might offer a viable treatment strategy. Tanshinone IIA and salviadione, both derived from Salviae Miltiorrhizae Radix et Rhizoma, possess anti-inflammatory and anti-oxidative activities. A series of new compounds were synthesized by hybridizing salviadione with tanshinone. Among these compounds, 15a showed beneficial effects in LPS-induced acute lung injury and diabetes-induced renal injury mouse models. The current study explored the therapeutic efficacy of 15a using both acute and chronic colitis models and elucidated the underlying mechanisms. DSS-induced colitis models were established in mice, where acute colitis was treated with compound 15a (5 or 10 mg·kg-1·d-1) for 8 days, while chronic colitis mice received compound 15a (5 or 10 mg·kg-1·d-1, i.g.) during 2.5% DSS administration. The 15a treatment significantly alleviated DSS-induced pathological and inflammatory damages in both acute and chronic colitis mouse models. In mouse intestinal epithelial cell line MODE-K, pretreatment with compound 15a (5 or 10 µM) significantly suppressed LPS + L18-MDP-induced inflammatory responses. The receptor-interacting serine/threonine kinase 2 (RIPK2) was identified as a direct binding target of compound 15a using microarrays and recombinant human proteins. Moreover, 15a could directly bind to and inhibit the phosphorylation of RIPK2, leading to the suppression of the NF-κB and MAPK signaling pathways. Furthermore, LEU153 and VAL32 were identified within the KD domain of RIPK2 as critical amino residues for the binding of 15a. Briefly, the current findings demonstrate that compound 15a holds promise as a therapeutic agent for managing acute and chronic colitis.